TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin; dioxin) is the most toxic man-made chemical. It has a broad range of toxic effects which are both species and tissue specific. Wasting, thymic atrophy, and delayed lethality are among its more common effects. It has also been shown to be a potent tumor promoter, both in the skin and liver. Polychlorinated dibenzofurans (PCDFs) act like TCDD and may be considered as "dioxin equivalents." In order to determine whether this class of compounds are also tumor promoters, and if the toxic equivalency factors derived from acute and short term studies apply to chronic effects, we are investigating the ability of 2,3,4,7,8-PentaCDF and 1,2,3,4,7,8-hexaCDF to promote MNNG-induced skin tumors in HRS hairless mice, in comparison to the results observed with TCDD. Recent studies on the mechanism of TCDD toxicity have indicated effects on certain growth modulating receptors, i.e., epidermal growth factors, glucocorticoid. We are investigating the effects of TCDD exposure on Transforming Growth Factor beta (TGF beta) and its receptor in hairless mouse skin, which has been shown to be a good model for chloracne, a sensitive indicator of TCDD toxicity in humans. We are also studying TGF and its receptors in a human squamous carcinoma line which is responsive to TCDD toxicity. Since effects on the growth factors (or receptors) may involve second messengers, we are initiating studies on the effects of TCDD on various second messenger systems.